The preparation of soft gelatin capsules has been extensively described, e.g., in Lachmann, Theory and Practice of Industrial Pharmacy, Lea and Febiger, Philadelphia, 2nd Edition. Therein it has been set forth that the type of the soft capsule filling materials is substantially restricted to three categories, namely water-immiscible, non-volatile or readily volatile carriers such as oils, fats, ethereal oils, chlorinated hydrocarbons, esters, ethers, higher alcohols and organic acids. Thus, this category of auxiliary and active ingredients is relatively easy to encapsulate and allows a rather wide margin for formulating the capsule sheath.
The second category comprises water-miscible non-volatile materials such as polyethylene glycols or emulsifiers. This category is much more difficult to process. Thus, the DE-OS No. 33 07 353, e.g., describes a process for preparing polyethyleneglycol-containing soft gelatin capsules, according to which process polyethyleneglycol can be reliably encapsulated only if quite well-defined parameters are maintained with respect to the capsule sheath as well as to the capsule fill material.
The problems encountered in encapsulating may be explained by that polyethyleneglycol-containing fillings will strongly interact with the capsule sheath and thus, the storage stability of the capsules is n longer readily ensured.
Finally, the third category comprises water-miscible and relatively low-volatile components such as, e.g., glycerol, propyleneglycol or benzyl alcohol. In this category the interactions described in the category (2) are so strong that components of the last category can only be encapsulated in concentrations of up to a maximum of 10%.
Rated to be not capable of being subjected to encapsulation, according to Lachmann, loc. cit., are liquids comprising more than 5% of water and lower molecular weight organic water-soluble compounds, more particularly lower alcohols such as ethyl alcohol, ketones and amines.
Particular problems are also involved in processing water-soluble or hygroscopic active substances in gelatin capsules, since these also adversely affect the capsule wall.